The objectives of this proposal are to investigate the roles of gastrointestinal hormones in the digestive processes. In this study, we will measure hormones with proven radioimmunoassay methods for gastrin, cholecystokinin, secretin and glucagon; we have in development specific radioimmunoassay methods for big gastrin, GIP, VIP, bombesin, and human and canine growth hormones. With these methods, we will determine the pattern of stimulated release of different gastrointestinal hormones (as well as different molecular forms of the individual hormones) in animals, in normal man, and in DU patients, before and after operation. We plan to study the interrelationship between gastrointestinal hormones and hormones of the pancreas and of the hypothalamic-hypophyseal axis by direct immunoassay measurements of circulating hormones. We will compare patterns of release of these hormones in response to a meal alone, and to a meal given in the presence of stimulated levels of other endogenous or exogenous hormones. We will study the influence of the Zollinger-Ellison syndrome and the syndrome of pancreatic cholera on the patterns of release of all measurable gastrointestinal hormones. We plan to study the mechanisms by which exogenously or endogenously elevated levels of gastrointestinal hormones are catabolized by different organs. We will determine more specifically the actions of gastrointestinal hormones by correlating their biologic activity with measurements of circulating concentrations of the hormones measured by radioimmunoassay. We plan a trial of CCK-therapy of ileus. We plan to grow ZE tumor cells and cells from different segments of gastrointestinal mucosa in tissue culture and to study the effects of various stimulating and inhibiting agents on the synthesis and release of gastrointestinal hormones. The storage patterns of individual gastrointestinal hormones in segments of gastrointestinal mucosa will be determined. Studies will be performed to answer the question of whether there is intraconversion among different molecular forms of hormones within the circulation.